Notes

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Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection and hospitalization in infants. Nirsevimab is a monoclonal antibody to the RSV fusion protein that has an extended half-life. The efficacy and safety of nirsevimab in healthy late-preterm and term infants are uncertain.

We randomly assigned, in a 21 ratio, infants who had been born at a gestational age of at least 35 weeks to receive a single intramuscular injection of nirsevimab or placebo before the start of an RSV season. The primary efficacy end point was medically attended RSV-associated lower respiratory tract infection through 150 days after the injection. The secondary efficacy end point was hospitalization for RSV-associated lower respiratory tract infection through 150 days after the injection.

A total of 1490 infants underwent randomization 994 were assigned to the nirsevimab group and 496 to the placebo group. Medically attended RSV-associated lower respiratory tract infection occurred in 12 infants (1.2%).
A single injection of nirsevimab administered before the RSV season protected healthy late-preterm and term infants from medically attended RSV-associated lower respiratory tract infection. (Funded by MedImmune/AstraZeneca and Sanofi; MELODY ClinicalTrials.gov number, NCT03979313.).
Consensus recommendations regarding the threshold levels of cardiac troponin elevations for the definition of perioperative myocardial infarction and clinically important periprocedural myocardial injury in patients undergoing cardiac surgery range widely (from >10 times to ≥70 times the upper reference limit for the assay). Limited evidence is available to support these recommendations.

We undertook an international prospective cohort study involving patients 18 years of age or older who underwent cardiac surgery. High-sensitivity cardiac troponin I measurements (upper reference limit, 26 ng per liter) were obtained 3 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We performed Cox analyses using a regression spline that explored the relationship between peak troponin measurements and 30-day mortality, adjusting for scores on the European System for Cardiac Operative Risk Evaluation II (which estimates the risk of death after cardiac surgery on the basis of 18 variables, including agenicalTrials.gov number, NCT01842568.).
The levels of high-sensitivity troponin I after cardiac surgery that were associated with an increased risk of death within 30 days were substantially higher than levels currently recommended to define clinically important periprocedural myocardial injury. (Funded by the Canadian Institutes of Health Research and others; VISION Cardiac Surgery ClinicalTrials.gov number, NCT01842568.).Welcome to the first issue of Community Dental Health to be published online only. The journal has been marching ahead now for many years and has reached unprecedented levels of recognition in several aspects of quality. Our Impact Factor (a measure of how often our papers are cited) has risen to its highest ever level of 1.349. A record 383 manuscripts were submitted last year, and as we can only publish 11% of this number, peer review and natural selection combine so that only the very best papers reach the readers.Objective To evaluate the short- and long-term effects of brexpiprazole on patient functioning in schizophrenia.Methods Data were included from three 6-week, randomized, double-blind, placebo-controlled studies (hospitalized patients); a 52-week, randomized, double-blind, placebo-controlled maintenance treatment study (terminated early by the study sponsor based on the positive result of an interim analysis); and two 52-week, open-label extension studies-all in patients with schizophrenia (DSM-IV-TR criteria) and conducted from July 2011-February 2016. Patients allocated to oral brexpiprazole received 2-4 mg/d (short-term studies) or 1-4 mg/d (long-term studies). Functioning was measured using the Personal and Social Performance (PSP) and Global Assessment of Functioning (GAF) scales, with response defined as a PSP/GAF increase of ≥ 10 points and remission as PSP score ≥ 71 or GAF score ≥ 61.Results Patients receiving brexpiprazole (n = 831) showed greater improvement than those receiving placebo (n = 490) fris were from studies with ClinicalTrials.gov identifiers NCT01396421, NCT01393613, NCT01810380, NCT01668797, NCT01397786, and NCT01810783.Objective Measurement-based care (MBC) improves patient outcomes. However, there has been minimal focus on MBC for psychotic disorders. This study examines the use of patient-reported outcome measures (PROMs) in the Veterans Health Administration (VHA) to characterize their use among Veterans with psychotic disorders and to inform candidate measures for psychosis-related MBC.Methods Data on Veterans with and without ICD-10 psychotic disorders and at least 1 PROM during fiscal years (FYs) 2016-2019 (FY16-FY19) were collected. The sample included 3,935,504 PROM administrations among 1,192,897 Veterans. Included PROMs spanned multiple symptom and non-symptom domains. Percentages of total PROM administrations were calculated by aggregating across time and diagnosis. Facility-level statistics were also calculated. Absolute change in the percentage of unique Veterans administered a particular and repeated PROMs over time were calculated.Results The core PROMs for VHA MBC (Patient Health Questionnaire-9 [PHQ-9], General Anxiety Disorder-7 Scale, PTSD Checklist-5, and Brief Addiction Monitor) accounted for the majority of PROMs for Veterans with (88.18%) and without (92.56%) psychotic disorders. The PHQ-9 accounted for the largest proportion (psychotic disorder 45.89%; other diagnosis 46.70%). The absolute changes in percentages of repeated PROM administration were similar over time across groups.Conclusions The use of PROMs in VHA mental health care increased during FY16-FY19 for Veterans with and without psychosis. The rates of PROM use were similar for both groups, and PROM use predominately consisted of the core measures. While the similar rates of PROM administration are encouraging, these findings highlight the need for psychosis-specific measures to tailor MBC for Veterans with these diagnoses.Objective Unwanted intrusive thoughts (UITs) of intentional infant-related harm are ubiquitous among new mothers and frequently raise concerns about infant safety. The purpose of this research was to assess the relation of new mothers' UITs of intentional, infant-related harm and obsessive-compulsive disorder (OCD) with maternal aggression toward the infant and to document the prevalence of maternal aggression toward the infant.Methods From a prospective, province-wide, unselected sample of 763 English-speaking postpartum women, a total of 388 participants provided data for this portion of the research. Participants completed 2 questionnaires and interviews postpartum to assess UITs of infant-related harm, OCD (based on DSM-5 criteria), and maternal aggression toward the infant. Data for this research were collected from February 9, 2014, to February 14, 2017.Results Overall, few participants (2.9%; 95% CI, 1.5% to 4.7%) reported behaving aggressively toward their infant. Participants who reported UITs of intentional, infant-related harm (44.4%; 95% CI, 39.2% to 49.7%) were not more likely to report aggression toward their newborn compared with women who did not report this ideation (2.6%; 95% CI, 0.9% to 5.8%; and 3.1%; 95% CI, 1.3% to 6.2%, respectively). The same was true for women with and without OCD (1.9%; 95% CI, 0.3% to 6.4%; and 3.5%; 95% CI, 1.8% to 6.0%), respectively.Conclusions This study found no evidence that the occurrence of either UITs of intentional, infant-related harm or OCD is associated with an increased risk of infant harm. The prevalence of child abuse of infants in this sample (2.9%) is lower than reported in others (4%-9%). Findings provide critical and reassuring information regarding the relation between new mothers' UITs of intentional harm and risk of physical violence toward the infant.The expression of the pluripotency factors OCT4, SOX2, KLF4, and MYC (OSKM) can convert somatic differentiated cells into pluripotent stem cells in a process known as reprogramming. Notably, partial and reversible reprogramming does not change cell identity but can reverse markers of aging in cells, improve the capacity of aged mice to repair tissue injuries, and extend longevity in progeroid mice. However, little is known about the mechanisms involved. Here, we have studied changes in the DNA methylome, transcriptome, and metabolome in naturally aged mice subject to a single period of transient OSKM expression. We found that this is sufficient to reverse DNA methylation changes that occur upon aging in the pancreas, liver, spleen, and blood. Similarly, we observed reversion of transcriptional changes, especially regarding biological processes known to change during aging. Finally, some serum metabolites and biomarkers altered with aging were also restored to young levels upon transient reprogramming. These observations indicate that a single period of OSKM expression can drive epigenetic, transcriptomic, and metabolomic changes toward a younger configuration in multiple tissues and in the serum.Ubiquitin (Ub) and its related small Ub like modifier (SUMO) are among the most influential protein post-translational modifications in eukaryotes. Unfortunately, visualizing these modifications in live cells is a challenging task. Chemical protein synthesis offers great opportunities in studying and further understanding Ub and SUMO biology. Nevertheless, the low cell permeability of proteins limits these studies mainly for in vitro applications. Here, we introduce a multiplexed protein cell delivery approach, termed MBL (multiplexed bead loading), for simultaneous loading of up to four differentially labeled proteins with organic fluorophores. We applied MBL to visualize ubiquitination and SUMOylation events in live and untransfected cells without fluorescent protein tags or perturbation to their endogenous levels. Our study reveals unprecedented involvements of Ub and SUMO2 in lysosomes depending on conjugation states. We envision that this approach will improve our understanding of dynamic cellular processes such as formation and disassembly of membraneless organelles.Seed dispersal directly affects plant establishment, gene flow and fitness. Understanding patterns in seed dispersal is, therefore, fundamental to understanding plant ecology and evolution, as well as addressing challenges of extinction and global change. Our ability to understand dispersal is limited because seeds may be dispersed by multiple agents, and the effectiveness of these agents can be highly variable both among and within species. We provide a novel framework that links seed dispersal to animal social status, a key component of behaviour. Because social status affects individual resource access and movement, it provides a critical link to two factors that determine seed dispersal the quantity of seeds dispersed and the spatial patterns of dispersal. compound 3i research buy Social status may have unappreciated effects on post-dispersal seed survival and recruitment when social status affects individual habitat use. Hence, environmental changes, such as selective harvesting and urbanisation, that affect animal social structure may have unappreciated consequences for seed dispersal.
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